This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. The Null-Mouse Core will maintain standing colonies of nuclear-receptor null-mice to serve the scientific needs of the five individual research projects, as well as those of the mentors and other investigators at the institution. Because numerous investigators will require nuclear-receptor null-mice, it is much more efficient and costeffective to have a "bank" of null-mice. The intent is to have 5 breeding pairs of each null strain in the nullmouse core. When an investigator needs to use a specific null mouse, three pairs of breeders will be transferred to the investigator, and the investigator will start paying the mouse maintenance. This will also save time because, MTAs (material transfer agreements) won't need to be obtained, nor income animals quarantine time. At the present time, we have the following null colonies: PXR, AhR, RXRa, CAR, PPARa, Nr'2, HNF1a, FXR (whole-body and hepatocyte-specific) and hepatocyte-specific PPARy and HNF4a. For the projects of this proposal, SHP-null mice will be obtained from David Moore at Baylor (Dr Wang's mentor). In addition, Core C will have the technical capability to engineer other new knockouts or double knockouts as needed. Another feature of this Core will be to conduct routine genotyping experiments necessary to demonstrate the ongoing integrity of the null-mouse model, as well as to engineer double-null mice, and perform the genotyping. The other major role of this core is to isolate liver, prepare hepatocytes, and perform culture experiments upon request for the investigators of this COBRE.